Results accumulated over the past several years have shown that there are significant deuterium isotope effects in oxidative dealkylation reactions when deuterium is substituted for hydrogen at the reacting center or an adjacent center. Other studies have shown that substitution with stable isotopes can decrease the carcinogenic potential of various carcinogens such as nitrosamines. We have therefore embarked on a program to determine the effect of such substitution on the toxicity of various drugs which might yield toxic metabolites by dealkylation. Such a study is under way with the analgesic drug phenacetin. Preliminary studies in vitro using chemical ionization mass spectrometry as an assay technique have revealed a significant deuterium isotope effect when deuterium was substituted for hydrogen at the reacting center (kH/kD 2). Additional studies are in progress to determine the possible effects in vivo of this deuterium substitution as well as the effects of deuterium substitution on the Beta-methyl group.